C10X polymorphism in the CARD8 gene is associated with bacteraemia
Version of Record online: 5 NOV 2013
© 2013 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Immunity, Inflammation and Disease
Volume 2, Issue 1, pages 13–20, June 2014
How to Cite
Asfaw Idosa, B., Sahdo, B., Balcha, E., Kelly, A., Söderquist, B. and Särndahl, E. (2014), C10X polymorphism in the CARD8 gene is associated with bacteraemia. Immunity, Inflammation and Dis, 2: 13–20. doi: 10.1002/iid3.14
This work was supported by Swedish Research Council (K2010-57X-21435-01-3), the Swedish Society of Medicine, the Research committee of the County Council of Örebro and Nyckelfonden at Örebro University Hospital.
- Issue online: 6 JUN 2014
- Version of Record online: 5 NOV 2013
- Manuscript Accepted: 27 SEP 2013
- Manuscript Revised: 19 SEP 2013
- Manuscript Received: 11 JUL 2013
- Swedish Research Council. Grant Number: K2010-57X-21435-01-3
- Swedish Society of Medicine
- Research committee of the County Council of Örebro and Nyckelfonden at Örebro University Hospital
- blood culture;
- gene variants;
- innate immunity;
The NLRP3 inflammasome is an intracellular multi-protein complex that triggers caspase-1 mediated maturation of interleukin-1β (IL-1β); one of the most potent mediators of inflammation and a major cytokine produced during severe infections, like sepsis. However, the excessive cytokine levels seem to stage for tissue injury and organ failure, and high levels of IL-1β correlates with severity and mortality of sepsis. Instead, recent data suggest caspase-1 to function as a guardian against severe infections. CARD8 has been implied to regulate the synthesis of IL-1β via interaction to caspase-1. In recent years, polymorphism of CARD8 (C10X) per se or in combination with NLRP3 (Q705K) has been implicated with increased risk of inflammation. The aim was to investigate the correlation of these polymorphisms with severe blood stream infection. Human DNA was extracted from blood culture bottles that were found to be positive for microbial growth (i.e. patients with bacteraemia). Polymorphisms Q705K in the NLRP3 gene and C10X in the CARD8 gene were genotyped using TaqMan genotyping assay. The results were compared to healthy controls and to samples from patients with negative cultures. The polymorphism C10X was significantly over-represented among patients with bacteraemia as compared to healthy controls, whereas patients with negative blood culture were not associated with a higher prevalence. No association was observed with polymorphism Q705K of NLRP3 in either group of patients. Patients carrying polymorphism C10X in the CARD8 gene are at increased risk of developing bacteraemia and severe inflammation.